Purpose: :
The Math5 (Atoh7) basic helix-loop-helix transcription factoris transiently expressed during early retinal histogenesis ina subset of newly post-mitotic precursors. These form 5% ofthe adult retina, including the first-born cell type, the retinalganglion cells (RGCs). Math5 is necessary, but not sufficient,for RGC development. In lineage tracing experiments, Math5+cells develop into all 7 major retinal cell types, and only10% become RGCs. Here, we investigate the role of Math5 as anRGC competence factor by expressing it in a wide populationof fate-restricted post-mitotic retinal precursors.

Methods: :
We generated Crx>Math5-ires-Cre mice using the 2.4 kb Crxpromoter to express Math5 and Cre recombinase from a singlebicistronic transcript. Previous Crx>Cre and Crx>lacZstudies show that Crx is normally expressed by photoreceptorsand bipolar cells, beginning shortly after terminal mitosis.We examined the properties and fates of Crx>Math5+ cellsat several time points during development, using the ROSA26-flox-GFPreporter.

Results: :
In 4 independent Crx>Math5-ires-Cre transgenic lines, weobserved lineage-labeled cells among all retinal cell types,including RGCs. In these mice, Cre and endogenous Crx are co-expressedin post-mitotic cells throughout development. Despite this large-scalereassignment of fates, involving 90% of the neural retina, RGCsare produced in normal abundance and have birthdates beforeP1. Adult photoreceptor and bipolar cells continue to expressMath5, but the retinal histology appears normal.